A porous biodegradable polymer scaffold is widely being used as a mold for the sake of various tissue regenerations. Such a scaffold requires a porous structure having a good coupling between pores so as to promote nutrition and oxygen supply for the sake of enough cell adhesion density, cell growth and differentiation.
There are various methods for preparing a porous biodegradable polymer scaffold, of which a pore formation particle porogen leaching is being most widely used. For the sake of pore formation particles, various particles, for example, salt, foamed salt, carbohydrate, hydrocarbon, wax, etc. are used. In the above method, a pore formation particle in a polymer/solvent/pore formation particle mixture is selectively melted or foamed, thus forming pores. In addition to the above method, there are an emulsion/freeze dry, a phase isolation method, an expansion of a threshold liquid phase, a 3D inkjet printing, etc. (A. G. Mikos, G. Sarakinos, S. M. Leite, J. P. Vacanti, R. Langer, Biomaterials, 14 (1993) 323-330; Z. Ma, C. Gao, Y. Gong, J. Biomed. Mater. Res. 67B (2003) 610-617; A. Park, B. Wu, L. G. Griffith, J. Biomater. Sci. Polym. Ed. 9 (1998) 89-110).
The porous polymer scaffold may be usefully used for the sake of recovery of bone, cartilage and liver. This scaffold is implemented in a human body through a surgical operation, which may entail a physical and economical burden to a patient. In order to minimize any inconvenience to the patient, a method for injecting a biodegradable polymer scaffold in an injection way is being developed. In this method, a polymer solution including cells is injected and is photo cross-linked or a hydro gel is formed based on a sol-gel phenomenon. (J. j. Marler, A. Guha, J. Rowley, R. Koka, D. Monney, J. Upton, J. p. Vacanti, Plast. Reconstr. Surg. 105 (2000) 2049-2058; S. He, M. J. Yaszemski, A. W. Yasko, P. S. Engel, A. G. Mikos, Biomaterials, 21 (2000) 2389-2394).
The hydro gel fails to provide an optimum environment to the cell which needs adhesion to a solid surface. Since a mechanical strength is weak, it is hard to protect cells embedded inside. In an effort to resolve the above mentioned problems, a wide range of natural and synthetic microparticles including cultispher which are microparticles made of gelatin having a porous structure is used for culture of animal cells, but its biological synthesis is bad, and a mechanical strength is not good enough.
The currently used method for preparing injection type microparticles is an emulsification-solvent evaporation method wherein a W/O/W double emulsification method is implemented through two emulsification stages. A porous structure is determined based on the safety of the W/O emulsion which is the first emulsification stage. Since emulsion is thermodynamically unstable, water phase and organic phase tend to isolate from each other through coalescence, fusion, creaming, etc., it is hard to prepare, which is a disadvantage. (M. Kanouni, H. L. Rosano, N. Naouli, Adv. Colloid Interface Sci. 99 (2002) 229-254; A. J. Webster, M. E. Cates, Langmuir, 14 (1998) 2068-2079).
In addition, there is a method for preparing a micro particle carrier wherein a W/O emulsion is formed in such a way to add an aqueous solution containing foamed salt to an organic phase wherein aliphatic polyester polymer is melted, and in a W/O/W double emulsification stage, a re-dispersion and emulsification are performed in an aqueous solution containing hydrophilic surface active agent (refer to Korean patent number 801194). The above micro particle carrier has a characteristic, for example, a degradability, a high porosity, and an interconnectivity between pores, etc., but a mechanical strength is weak, and mass production is hard.
In a recently developed method for preparing a biodegradable polymer micro particle, a biodegradable polymer is dissolved in a DMSO (Dimethyl Sulfoxide) and is sprayed onto a low temperature hydrocarbon solution, and a DMSO/polymer solution is frozen, and a DMSO is removed from a low temperature salt aqueous solution, thus preparing biodegradable polymer microparticles (refer to Korean patent number 1105292). The thusly prepared microparticles have high porosity and good mechanical strength and good cell affinity. However, it has a problem in that hydrocarbon should be used as a freezing solution during the spraying process which is the most important process among the manufacturing processes. Hydrocarbon has a low ignition point, which means a high danger of fire. So, such a method is not easy to use for the sake of mass production. To this end, developments on a new preparation process which is able to resolve the above mentioned problems is inevitable.
Therefore, it urgently needs to develop a less danger and environment friendly mass production process which is able to prepare polymer microparticles having good biological suitability, biodegradability, porosity, mechanical strength, and cell affinity.